The eukaryotic metaphase chromosome represents an approximately 10 to the 4th power-fold condensation of DNA. This condensation is probably achieved by several orders of DNA packing, each order dependent on unique DNA and protein interactions. The relationship of the nature of DNA packaging to cytological chromosome analysis techniques (i.e., G-banding) has not been established. The goal of this research is to characterize the interactions which stabilize DNA-folding in metaphase chromosomes and relate this to the banding patterns observed in the analysis of human metaphase chromosomes. An understanding of metaphase chromosome structure may lead to more detailed analysis of human chromosomes by the standard techniques, as well as new methods of analysis based directly on chromosomal protein content. The strategy of this research is to combine defined molecular probes of alterations with cytological observations. A portion of the work will deal with probes of isolated chromosomes in solution followed by biochemical and cytological analysis. In addition, antibodies to non-histone chromosomal proteins will be used to investigate the distribution of these proteins on metaphase chromosomes.